| BackgroundIn 2002,the International urinary Control Association(?International Continence Society,ICS?defined bladder hyperactivity syndrome?Overactive Bladder,OAB?as a syndrome characterized by urgent urination,often with frequent urination and nocturnal urination,with or without urgent urinary incontinence,but excluding urinary tract infection or other pathophysiological changes.OAB is a common syndrome that increases with age and affects quality of life.It is estimated that 50 million to 100 million people worldwide suffer from OAB.According to the 2003 NOBLE plan survey in the United States,the prevalence rate of OAB in men and women over the age of 18 was16.0%and 16.9%respectively.At the same time,women with urgent urinary incontinence were more common,and the incidence of urgent urinary incontinence in women increased significantly after the age of 44.A 2004 Canadian survey of 3249adults aged 35 and older showed that the prevalence of OAB was 18.1%,with males?14.8%?lower than females?21.2%?.The EPIC study published in 2006 pointed out that among people over 18 years old in five European countries,the prevalence rate of OAB was 11.8%,the ratio of men and women was similar,and the prevalence rate increased with age.A survey of 14844 patients in six regions in China in 2011 showed that the prevalence of OAB in China was 6.0%?5.9%for men and 6.0%for women?,and women were significantly more likely to develop urgent urinary incontinence after the age of 50.At present,the pathogenesis of OAB is not clear.OAB symptoms such as frequent urination and urgent urination will bring trouble to our normal life and work,affect our physical and mental health,and cause a huge psychological burden.At present,behavioral therapy and drug therapy are the first choice for the treatment of OAB.The most commonly used drugs are M receptor antagonists,including solinaxine,piperidine,tolterodine,oxybutynin,troxonium chloride,fesorodine fumarate and so on.However,M receptor antagonists may cause dry mouth,blurred vision,constipation,urinary retention and so on,which seriously reduce the medical compliance of patients.Clinical behavior training combined with drugs in the treatment of OAB,but some patients adhere to oral drugs,the effect is not good?lack of efficacy or/and can not tolerate adverse reactions of drugs?,these are called refractory OAB patients.At present,patients with refractory OAB are mainly treated with botulinum toxin A(Botulinum Toxin Type A?BTX-A?detrusor injection,sacral neuroregulation and bladder enlargement.But after all,it is invasive,complex operation,high medical costs and hospitalization,it is not easy for patients to accept,and easy to lead to postoperative iatrogenic infection.With the progress of the disease,the quality of life of OAB patients also decline,and affect the mental health of patients,causing anxiety,depression and other psychological problems.Studies have shown that about 30%to 40%of OAB patients have the above psychological problems.And after long-term drug treatment is not effective in refractory OAB patients,easy to breed anxiety.Amitriptyline hydrochloride tablets,as tricyclic antidepressants,have antidepressant,anxiety,sedative and anticholinergic effects.For patients with long-term busyness,the choice of amitriptyline hydrochloride tablets is simple,convenient,low cost,non-invasive,does not need to be hospitalized,and is more easily accepted.However,there are no reports about amitriptyline hydrochloride alone in the treatment of OAB at home and abroad.Therefore,we conducted a prospective,randomized controlled study on refractory OAB patients who were treated in the urology clinic of our hospital from July 2019 to January2020 to evaluate the efficacy and safety of amitriptyline hydrochloride in the treatment of refractory OAB,so as to provide a basis for clinical use of amitriptyline hydrochloride in the treatment of refractory OAB.PurposeTo explore the clinical efficacy and safety of oral amitriptyline hydrochloride in the treatment of refractory OAB,and to provide new ideas and basis for the treatment of OAB.Research methods1.Inclusion criteria:?1?meet the OAB diagnostic criteria defined by ICS in 2002,symptoms characterized by urgent symptoms,often with frequent urination and nocturnal symptoms,with or without urgent urinary incontinence;?2?the course of disease?3months;?3?poor effect after behavioral training and anticholinergic treatment?lack of efficacy or/and adverse reactions that could not be tolerated?;?4?able to understand this research project and sign informed consent form.2.Exclusion criteria:?1?urinary tract infection within 2 months;?2?neurogenic bladder;?3?bladder pain syndrome/interstitial cystitis;?4?lower urinary tract symptoms/lbpieevlenvriigc n fs uunprrgocteistroaynt;e?8?o TbdBsitraIubLce ttie>osn;?9?1?5?.h5 ius rtio×nra yr nyoof rtrdmaracultg nuuespoe;pepl?10?rasn malrisr;m oi?6?wt uarnUignlLaer Nyg</sub>l,ac aulcAcoSulmTi;a/;A?7??11?L Thai bstn>oorr ym o2.a5fl×ULNcGounasnegnzt;hf?12?aooru bmf.norirst peomal renaple's Hl ospital)function;?13?pre(?SCr>?gna n1.5cy×/ULNlactati,o nD;e?14?refusingpartment toof signLabo informratory edoff All the selected patients should follow the experimental scheme strictly and adopt the random method of"=RAND??function".The control group and the experimental group were given 1/2,and the control group was given the replacement of unused muscarinic receptor antagonists.Such as Solina Succinate tablets?trade name:Weixikang;oral,5mg,once a day,oral for 4 weeks?,oxybutynin hydrochloride capsules?trade name:Jiesai;oral,5mg,twice a day,oral for 4 weeks?,tolterodine tartrate tablets?trade name:sernitin;oral,2mg,twice/d,oral for 4 weeks?,propivacine hydrochloride sustained release capsules(trade name:maitonol;Oral administration,30mg,once a day,for 4weeks.The experimental group was given amitriptyline hydrochloride tablets?12.5 mg,twice a day,and the dose could be increased to 25 mg,3 times a day for 4 weeks?.All the selected patients recorded voiding diaries 3 days before treatment and 3 days before each revisit.The following indexes were measured before treatment,2 weeks after treatment and 4 weeks after treatment:average daily micturition times,average nocturnal urination times,average 24-hour urination times,average 24-hour urinary incontinence times,Quality of Life?QOL?,International Consultation on Incontinence Questionnaire Short Form?ICI-Q-SF?,King's Health Questionnaire?KHQ?,Symptom score of overactive bladder?OABSS?,self-rating anxiety scale?Self-rating Anxiety Scale,SAS?,self-rating depression scale?Self-rating Depression Scale,SDS?,adverse events.The statistical results were inputted by Excel software and analyzed by SPSS16.0statistical software.The measurement data were expressed by mean±standard deviation.T-test of two independent samples was used for comparison between groups.Rank sum test was used for variance inequality.Pairwise t-test was used to compare the data of each group,and the difference did not conform to normal distribution,then rank sum test was used.The chi-square test of binary data was used to compare the adverse events,P<0.05indicates that the difference is statistically significant,and P<0.01 indicates that the difference is extremely significant.This scheme has been approved by the hospital ethics committee.ResultFrom July 2019 to January 2020,32 patients with refractory OAB were diagnosed in the outpatient clinic of the researchers,including 30 patients,20 patients in the experimental group and 10 patients in the control group.No shedding cases were found.8 males?26.67%?and 22 females?73.33%?.The age of experimental group and control group was 39.45±12.424 years old and 46.10±10.826 years old respectively,the course of disease was 79.00±78.207months and 70.20±65.973 months,the OABSS scores before treatment were 8.60±2.062 and 8.70±2.263,the scores of KHQ?subtable 1?before treatment were 451.55±204.024 and 398.50±167.453 respectively,and the scores of KHQ?subtable 2?before treatment were 8.10±2.654 and 7.90±2.283 respectively.The QOL scores,SAS scores,SDS scores,daily micturition times,nocturnal micturition times and nocturnal urination times before treatment were 0.725±0.725,43.40±9.949,45.20±14.377,38.30±11.295,13.70±7.057,12.40±3.134 and 3.70±2.179,2.60±1.350,respectively,and the average nocturnal micturition times in the first three days were 3.70±2.179,2.60±1.350,respectively,and the average nocturnal urination times in the first three days were 3.70±2.179,2.60±1.350,respectively,and the average nocturnal urination times in the first three days were 3.70±2.179,2.60±1.350,respectively.The average times of urination in the first three days were 8.15±7.322 and 5.20±3.910respectively.There was no significant difference between the two groups by bilateral t-test or rank sum test?P>0.05?.The results of 2 and 4 weeks after treatment in the experimental group:the average daytime micturition times,nocturnal micturition times,emergency times and OABSS scores were 10.20±4.503,1.65±1.137,1.30±1.081,3.50±3.411,2.05±2.235,KHQ?and 298.20±175.917,233.50±132.272,respectively.KHQ scores were 5.50±2.140 and4.00±2.077 respectively,QOL scores were 3.35±0.988 and 2.65±0.93 respectively,and QOL scores were 35.65±7.856 and 32.15±5.294 respectively.Compared with those before treatment,the above-mentioned indexes were significantly improved,P<0.05.The above-mentioned indexes were significantly improved as compared with those before treatment,and the differences were statistically significant.It is concluded that amitriptyline can not only improve the symptoms of OAB,but also improve the quality of life of patients,but also improve anxiety and depression.Pairwise comparison of various indexes between 4 weeks and 2 weeks after treatment in the experimental group:There were significant differences in average daily micturition frequency,average urgent micturition frequency,OABSS score,KHQ?sub-table 1?score,KHQ?sub-table 2?score,QOL score,SAS score and SDS score?P<0.05?.There was no significant difference in the average number of nocturnal urination?P>0.05?.It was concluded that amitriptyline hydrochloride tablets began to improve in the second week and further improved in the fourth week.The results of 2 weeks and 4 weeks after treatment in the control group:the average daily micturition times were 11.00±3.266 and 10.20±3.155,respectively.The scores of KHQ?subtable 1?were 383.80±166.563 and 362.60±181.575,respectively.The above indexes were significantly improved compared with those before treatment,and the differences were statistically significant,P<0.05.The average frequency of urination,OABSS score and KHQ score were significantly improved 4 weeks after treatment,which were 3.20±2.348,6.90±1.197 and 6.10±1.524,respectively,P<0.05.There was no significant difference in the average number of nocturnal urination,QOL score and SDS score between 2 weeks and 4 weeks after treatment?P>0.05?.It is concluded that the replacement of M receptor antagonist can still improve the symptoms of OAB,but can not improve the symptoms of anxiety and depression and improve the quality of life of patients.Pairwise comparison of various indexes between 4 weeks and 2 weeks after treatment in the control group:There were significant differences in the average frequency of urination,KHQ?sub-table 1?score and KHQ?sub-table 2?score?P<0.05?.There was no significant difference in average daily micturition frequency,OABSS score and SAS score.?P>0.05?.The results showed that the replacement of M receptor antagonist in the control group began to improve in the 2nd week and further improved in the 4th week.Comparison of the changes between the two groups in the same period after treatment:in the second week,the scores of OABSS,KHQ?sub-table 1?,KHQ?sub-table 2?,QOL,SAS,SDS,average nocturnal urination and average urgent urination in the experimental group were significantly better than those in the control group,and the difference was statistically significant?respectively-31.14%vs-11.75%,P=0.017;-35.32%vs-3.78%,P<0.001;-31.78%vs-11.75%,P=0.008;-32.67%vs-6.00%,P<0.001;-16.68%vs-4.90%,P=0.006;-14.90%vs-0.66%,P=0.001;-49.51%vs-6.50%,P=0.002;-57.54%vs-12.33%,P=0.002?.There was no significant difference in the improvement of the average daily micturition times between the experimental group and the control group?-21.79%vs-11.44%,P=0.074?.At the 4th week,the improvement of OABSS score,KHQ?sub-table 1?score,KHQ?sub-table 2?score,QOL score,SAS score,SDS score,average daytime micturition frequency,average nocturnal micturition frequency and average urination frequency in the experimental group were better than those in the control group,and the difference was statistically significant?respectively-48.73%vs-17.10%,P=0.001;-47.03%vs-10.81%,P<0.001;-52.27%vs-19.41%,P<0.001;-46.08%vs-14.50%,P=0.001;-23.50%vs-5.95%,P=0.01;-19.72%vs-1.76%,P<0.001;-32.50%vs-17.48%,P=0.035;-56.75%vs-13.17%,P<0.001;-78.57%vs-34.67%,P<0.001?.According to the OABSS questionnaire,the treatment effective rate of the experimental group was significantly higher than that of the control group,which was 65%and 20%,respectively,and the difference was statistically significant?P=0.02?.As a result,it is concluded that the improvement degree of the experimental group is better than.During the treatment period,7 cases in the control group were treated with sulinaxine before the trial,4 cases were replaced with piperidine after the trial,3 cases were replaced with tolterodine,and 2 cases in the control group were treated with propivacillin before the trial and tolterodine after the trial.1 case in the control group was treated with tolterodine before the trial and changed after the trial.In the experimental group,in the second week after the trial,the dose of amitriptyline increased gradually from the initial 12.5mg?twice a day?to 25mg?three times/d?;?,13 patients in the experimental group did not change the dose?12.5mg twice a day?.During the treatment,there were 3 cases of dry mouth,8 cases of slight dizziness in the morning,2 cases of constipation and 1 case of tongue numbness in the experimental group.In the control group,there were 3 cases of xerostomia,1 case of constipation,the symptoms were bearable and did not change the dose,and 2 cases had dysuria?female,age 45 and 57years old,respectively?.The symptoms were improved after 3 days of withdrawal and replaced with other M receptor antagonists?the symptoms of dysuria were alleviated after changing pipivacillin into tolterodine?.There was no significant difference in the incidence of adverseConclusionBoth amitriptyline hydrochloride tablets and replacement of M receptor antagonists can improve the symptoms of refractory OAB and anxiety with good safety,but the curative effect of amitriptyline hydrochloride is better than that of M receptor antagonists and has antidepressant effect. |
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